Elobixibat delivers superior symptom relief and quality-of-life improvements compared with prucalopride in the second-line treatment of patients with functional constipation, as shown in a head-to-head trial.
“While both agents produced robust improvements in several patient-reported outcomes after 8 weeks of treatment,” the rate of sustained complete spontaneous bowel movement (CSBM) response—the primary endpoint—was significantly higher with elobixibat vs prucalopride, according to the investigators.
Defined as at least three CSBMs per week and an increase of at least one CSBM from baseline for at least 6 of 8 weeks, sustained CSBM response was achieved by 55.6 percent of patients in the elobixibat group vs 33.9 percent of those in the prucalopride group (p=0.024). [Aliment Pharmacol Ther 2026;doi:10.1111/apt.70828]
At week 8, elobixibat-treated patients also showed greater improvement in key symptom domains, including straining (mean change, −2.1 vs −1.1; p<0.001), abdominal discomfort (mean change, –1.9 vs –1.1; p=0.005), bloating severity (mean change, –1.2 vs –0.6; p=0.011), and quality of life as assessed using the Validated Patient Assessment of Constipation Quality of Life scale (mean change, –9.3 vs –4.6; p=0.009).
“Both treatments were well tolerated,” the investigators noted.
Adverse events (AEs) occurred in 10.2 percent of patients receiving elobixibat and 8.5 percent of those receiving prucalopride. Most AEs were mild, with a similar incidence between the two treatment groups. The most common AEs were abdominal pain, diarrhoea, abdominal distension, and dyspepsia.
“In summary, our findings suggest that elobixibat, an ileal bile acid transporter (IBAT) inhibitor with a dual secretory and prokinetic mechanism, may represent a more effective second-line therapeutic option for functional constipation compared with prucalopride,” the investigators said.
They pointed out that the greater efficacy of elobixibat may be attributed to its dual mechanism of action. Unlike the highly selective 5-HT4 receptor agonist prucalopride that accelerates colonic transit but does not directly affect luminal fluid secretion, elobixibat exerts its effect on constipation through secretion of fluid and promotion of large intestinal motility. [Ther Clin Risk Manag 2021;17:601-615; Expert Opin Pharmacother 2018;19:1381-1388; Expert Rev Gastroenterol Hepatol 2018;12:951-960]
“By delivering more fluid to the colon and speeding transit, [elobixibat] likely produces softer stools and more complete evacuations, whereas a pure motility agent may leave some stools firm or incompletely passed,” the investigators explained. “These reinforce the importance of targeting multiple pathophysiological pathways in a heterogeneous disorder such as functional constipation.”
The trial was conducted in India and included 214 adult patients meeting Rome IV criteria for functional constipation and refractory to first-line treatment. After a standardized run-in period, these patients were randomly assigned to receive treatment with either elobixibat 10 mg (n=108) or prucalopride 2 mg (n=106), administered orally once daily for 8 weeks.
The mean age of the patients was 50.8 years, and 62.6 percent were male. The baseline frequency of CSBMs was low at a mean of 0.9 per week in both treatment groups. Symptom severity scores for straining, abdominal discomfort, bloating and feeling of incomplete evacuation, and stool consistency scores were similar between the elobixibat and prucalopride groups.
“Future research should prioritize long-term head-to-head comparisons across mechanistically distinct second-line therapies, including enterokinetics, IBAT inhibitors, and secretagogues, in both randomized and real-world settings,” according to the investigators.
“Delineating patient subgroups, such as slow-transit vs normal-transit constipation or irritable bowel syndrome with constipation vs functional constipation, that derive differential benefit from specific drug classes will be essential to optimize individualized treatment algorithms and improve long-term outcomes,” they added.